Our major goal is to analyze the regulatory mechanism of the T-cell-receptor gene through the analysis of DNase I hypersensitive sites. In addition, by comparison of normal and abnormal regulation of the T-cell--receptor gene we may define a mechanism related to the T cell disorder seen in autoimmune mice. The objective can be achieved with the following specific aims: 1. To analyze DNase I hypersensitive sites in the T-cell-receptor alpha, beta, and gamma chain in the mouse. The DNase I hypersensitive sites will be sequenced and compared with each other and to the immunoglobulin DNase I hypersensitive sites. 2. To evaluate developmental changes of DNase I hypersensitive sites which accompany T cell development. Using cell lines, tumor cells, and hybridomas the relationship between DNase I hypersensitive site and expression / rearrangement will be studied. 3. To define nuclear proteins binding to DNA near DNase I hypersensitive sites of the T-cell receptor gene. We will study whether DNA binding protein exists for the beta chain J-C introns. 4. To study T-cell-receptor disorders in autoimmune mice to help understand certain aspects of the process. We have recently observed a disorder of rearrangement and expression in T-cell-receptor genes in autoimmune mice. We will study the genetic disorder mechanism involving T-cell-receptor gene by investigating the DNase I hypersensitive sites and the DNA binding proteins.